1. Field of the Invention
The present invention relates to a CCD-based biochip reader, particularly to a biochip reader with a charge-coupled device (CCD) camera to collect and analyze images of fluorescence from biochips.
2. The Prior Arts
Tools and methods are designed to detect and analyze nucleic acids and proteins in the cellular and molecular biology field. However, it takes much time to complete analysis of a large number of samples. Moreover, errors arise since so many samples cannot be analyzed at the same time. For accelerating the progress of the related research, especially the genomic and proteomic research, high-throughput tools for efficient analysis are manufactured, of which an example is biochips. Biochips are applied to gene expression, drug selection and disease diagnosis in both basic research and clinical application fields.
There are three kinds of biochips that are currently known as DNA chip, lab-on-a-chip and protein chip. Since the protein chip and the lab-on-a-chip are difficult to operate, the DNA chip is in common use now. The detection of the DNA chip is shown in FIG. 1. First, known DNA fragments used as DNA probes (2) are immobilized onto the surface of a glass slide or a silicon chip and form a DNA chip (1). Generally, the DNA probes (2) arranged in array are called a DNA microarray. On the other hand, unknown DNA fragments (3), the target DNA, are labeled with fluorophores. The DNA chip (1) is hybridized with target DNA (3). After steps of washing, only DNA fragments hybridized with DNA probe are left on DNA chip (1). By scanning the DNA chip with a biochip reader, the fluorescence excited from the fluorophores is detected and the obtained hybridization result is analyzed.
Generally, a conventional biochip reader relies on laser excitation and a photomultiplier tube for detector (laser/PMT based systems) is employed to obtain representative images. FIG. 2 is a schematic view showing an example of the conventional biochip reader (4). Light beams emitted from a laser source (40) pass through a focusing lens (41), reflected by a beam splitter (42), and then passing through another focusing lens (43) to a surface of the biochip (44). The fluorescent dyes on the biochip (44) are excited by the light beams and in turn emit fluorescence (45). The fluorescence (45) passes through the focusing lens (43), the beam splitter (42), and the other focusing lens (46). The fluorescence (45) further passes through a filter (47), with which the light beams from the light source are filtered out. A detected photo signal is transmitted to a photomultiplier tube (PMT) (48), which converts the light pulse into an amplified electrical signal. Finally, the signal is fed to a computer (49) and processed to form image data. In the prior art biochip reader, to obtain the final result requires scanning all samples on the biochip, converting light pulses into electrical signals, and forming the electrical signal image data for analysis. The prior art biochip is disadvantageous for it takes a long time to scan all the samples and obtain the images.
The other kind of biochip reader uses white-light excitation with a high-pixel charge-coupled device (CCD) camera to collect images and analyze. Although it is not necessary to scan all the samples on the biochip in this kind of biochip reader, the white-light excitation is not efficient and the sensitivity is lower than the laser/PMT based systems. To enhance sensitivity, it takes a long time to obtain a more intensive fluorescent signal.
As mentioned above, the utility of the biochip analysis system will be increased if the results of the biochip reader are analyzed efficiently.